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Acta Cryst. (2009). E65, o564-o565    [ doi:10.1107/S1600536809005029 ]

5-Acetyl-4-(4-chlorophenyl)-6-methyl-3,4-dihydropyrimidine-2(1H)-thione

N. Anuradha, A. Thiruvalluvar, K. Pandiarajan, S. Chitra and R. J. Butcher

Abstract top

In the title molecule, C13H13ClN2OS, the heterocyclic ring adopts a flattened boat conformation, and the plane through the four coplanar atoms makes a dihedral angle of 87.92 (10)° with the benzene ring. The thione, acetyl and methyl groups have equatorial orientations with respect to the attached heterocyclic ring. The chlorophenyl group has an axial orientation. Intermolecular N-H...O, N-H...S and C-H...O hydrogen bonds are found in the crystal structure.

Comment top

Dihydropyrimidin-2(1H)-ones are pharmacologically acitive as antioxidant agents (Stefani et al., 2006). In recent years, much research has been focused on the synthesis of dihydropyrimidinones, which are important compounds due to their therapeutic and pharmacological properties. For example, they can serve as the integral of several calcium channel blockers (Rovnyak et al., 1995; Atwal et al., 1990), antihypertensive agents (Atwal et al., 1991; Grover et al., 1995). Recently, some marine alkaloids possessing dihydropyrimidine-5-carboxylate core have been shown to exhibit interesting biological activities such as potent HIV-gp-120-CD4 inhibitors as well as anti-HIV agents (Patil et al., 1995). Dihydropyrimidin-2(1H)-thiones are also of much interest with regard to biological activity (Kappe, 1993).

In the title molecule, C13H13ClN2OS, Fig.1., the heterocyclic ring adopts a flattened boat conformation, and the plane through the four coplanar atoms(C2,N3,C5 and C6) makes a dihedral angle of 87.92 (10)° with the benzene ring. The thione, acetyl and methyl groups have equatorial orientation, with the attached heterocyclic ring. The chlorophenyl group has an axial orientation. N1—H1···O15(1 + x, y, z), N3—H3···S2(2 - x, 1 - y, 1 - z) and C61—H61B···O15(1 + x, y, z) intermolecular hydrogen bonds are found in the crystal structure(Fig.2., Table 1).

Related literature top

For dihydropyrimidin-2(1H)-ones as anti-oxidant

agents, see: Stefani et al. (2006), and for their biological activity, see: Patil et al. (1995). For dihydropyrimidinones as calcium channel blockers, see: Rovnyak et al. (1995); Atwal et al. (1990) and as antihypertensive agents, see: Atwal et al. (1991); Grover et al. (1995). For the biological activity of marine alkaloids possessing a dihydropyrimidine-5-carboxylate core, see: Kappe (1993).

Experimental top

A solution of acetylacetone (1.0012 g, 0.01 mol), 4-chlorobenzaldehyde (1.40 g, 0.01 mol) and thiourea (1.14 g, 0.015 mol) was heated under reflux in the presence of calcium fluoride (0.07 g, 0.001 mol) for 2 h (monitored by TLC). After, completion of the reaction, the reaction mixture was cooled to room temperature and poured into crushed ice. The solid product was filtered under suction and purified by recrystallization from hot methanol to gave the product in the pure form. Yield 1.02 g (90%).

Refinement top

H1 at N1 and H3 at N3 atoms were located in a difference Fourier map and refined isotropically. Remaining H atoms were positioned geometrically and allowed to ride on their parent atoms, with C—H = 0.93 - 0.98 Å and Uiso(H) = 1.2 - 1.5 times Ueq(C).

Computing details top

Data collection: CrysAlis CCD (Oxford Diffraction, 2008); cell refinement: CrysAlis RED (Oxford Diffraction, 2008); data reduction: CrysAlis RED (Oxford Diffraction, 2008; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound, showing the atom-numbering scheme and displacement ellipsoids drawn at the 30% probability level. H atoms are shown as small spheres of arbitrary radius.
[Figure 2] Fig. 2. The packing of the title compound, viewed down the a axis. Dashed lines indicate hydrogen bonds. H atoms not involved in hydrogen bonding have been omitted.
5-Acetyl-4-(4-chlorophenyl)-6-methyl-3,4-dihydropyrimidine-2(1H)-thione top
Crystal data top
C13H13ClN2OSZ = 2
Mr = 280.77F(000) = 292
Triclinic, P1Dx = 1.331 Mg m−3
Hall symbol: -P 1Melting point: 529.5 K
a = 7.2389 (6) ÅCu Kα radiation, λ = 1.54184 Å
b = 8.2304 (7) ÅCell parameters from 2326 reflections
c = 12.9038 (11) Åθ = 5.9–77.2°
α = 73.366 (7)°µ = 3.72 mm−1
β = 89.373 (7)°T = 295 K
γ = 72.613 (7)°Prism, colourless
V = 700.62 (11) Å30.42 × 0.25 × 0.22 mm
Data collection top
Oxford Diffraction Gemini R
diffractometer		2878 independent reflections
Radiation source: fine-focus sealed tube2105 reflections with I > 2σ(I)
graphiteRint = 0.036
Detector resolution: 10.5081 pixels mm-1θmax = 77.4°, θmin = 5.9°
φ and ω scansh = −9→5
Absorption correction: multi-scan
(CrysAlis RED; Oxford Diffraction, 2008)		k = −10→9
Tmin = 0.182, Tmax = 1.000l = −16→16
6666 measured reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.071Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.202H atoms treated by a mixture of independent and constrained refinement
S = 1.03 w = 1/[σ2(Fo2) + (0.1275P)2 + 0.1258P]
where P = (Fo2 + 2Fc2)/3
2878 reflections(Δ/σ)max = 0.001
173 parametersΔρmax = 0.53 e Å−3
0 restraintsΔρmin = −0.23 e Å−3
Crystal data top
C13H13ClN2OSγ = 72.613 (7)°
Mr = 280.77V = 700.62 (11) Å3
Triclinic, P1Z = 2
a = 7.2389 (6) ÅCu Kα radiation
b = 8.2304 (7) ŵ = 3.72 mm−1
c = 12.9038 (11) ÅT = 295 K
α = 73.366 (7)°0.42 × 0.25 × 0.22 mm
β = 89.373 (7)°
Data collection top
Oxford Diffraction Gemini R
diffractometer		2878 independent reflections
Absorption correction: multi-scan
(CrysAlis RED; Oxford Diffraction, 2008)		2105 reflections with I > 2σ(I)
Tmin = 0.182, Tmax = 1.000Rint = 0.036
6666 measured reflectionsθmax = 77.4°
Refinement top
R[F2 > 2σ(F2)] = 0.071H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.202Δρmax = 0.53 e Å−3
S = 1.03Δρmin = −0.23 e Å−3
2878 reflectionsAbsolute structure: ?
173 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
Special details top

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Cl10.5516 (3)0.8292 (2)−0.08141 (12)0.1388 (8)
S21.30462 (11)0.38375 (11)0.46485 (8)0.0548 (3)
O150.6554 (3)0.0586 (3)0.3317 (3)0.0656 (9)
N11.2495 (3)0.1540 (3)0.3701 (2)0.0469 (8)
N30.9758 (3)0.3326 (3)0.4163 (2)0.0449 (8)
C21.1665 (4)0.2871 (4)0.4144 (3)0.0429 (8)
C40.8486 (4)0.2810 (4)0.3534 (3)0.0418 (8)
C50.9546 (4)0.1023 (4)0.3372 (3)0.0410 (8)
C61.1509 (4)0.0490 (4)0.3417 (2)0.0410 (8)
C150.8251 (4)0.0061 (4)0.3157 (3)0.0467 (9)
C160.8904 (5)−0.1503 (5)0.2717 (4)0.0669 (13)
C410.7733 (5)0.4234 (4)0.2449 (3)0.0486 (9)
C420.8999 (6)0.4851 (5)0.1744 (3)0.0681 (12)
C430.8321 (8)0.6118 (6)0.0741 (4)0.0832 (16)
C440.6360 (9)0.6762 (6)0.0464 (4)0.0843 (16)
C450.5095 (8)0.6201 (7)0.1132 (5)0.0967 (19)
C460.5777 (6)0.4951 (6)0.2145 (4)0.0738 (16)
C611.2863 (4)−0.1154 (4)0.3226 (3)0.0563 (12)
H11.367 (5)0.131 (4)0.361 (3)0.040 (8)*
H30.910 (5)0.415 (5)0.448 (3)0.058 (10)*
H40.736850.268460.394900.0500*
H16A0.78061−0.186850.259150.1003*
H16B0.98424−0.247150.323240.1003*
H16C0.94799−0.117070.204720.1003*
H421.032600.440970.194390.0819*
H430.918060.651790.026920.0998*
H450.377130.664300.092170.1159*
H460.489600.459900.261950.0886*
H61A1.25700−0.218510.367240.0843*
H61B1.41785−0.124020.340800.0843*
H61C1.27086−0.109090.247640.0843*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.2014 (19)0.0993 (10)0.0671 (8)−0.0081 (12)−0.0255 (10)0.0105 (7)
S20.0423 (4)0.0610 (5)0.0724 (6)−0.0201 (3)0.0039 (3)−0.0325 (4)
O150.0355 (11)0.0666 (14)0.105 (2)−0.0201 (10)0.0099 (12)−0.0365 (14)
N10.0286 (11)0.0521 (14)0.0644 (17)−0.0132 (10)0.0056 (10)−0.0232 (12)
N30.0377 (12)0.0493 (13)0.0526 (15)−0.0123 (10)0.0049 (10)−0.0238 (12)
C20.0392 (14)0.0462 (14)0.0448 (16)−0.0147 (12)0.0011 (12)−0.0141 (12)
C40.0353 (13)0.0450 (14)0.0465 (16)−0.0120 (11)0.0055 (11)−0.0164 (12)
C50.0373 (13)0.0388 (13)0.0467 (16)−0.0110 (10)0.0029 (11)−0.0133 (12)
C60.0368 (13)0.0406 (13)0.0465 (16)−0.0135 (11)0.0033 (11)−0.0126 (11)
C150.0375 (14)0.0459 (15)0.0549 (18)−0.0152 (12)−0.0018 (12)−0.0094 (13)
C160.0512 (18)0.064 (2)0.098 (3)−0.0223 (16)0.0000 (19)−0.038 (2)
C410.0530 (16)0.0433 (15)0.0510 (18)−0.0114 (12)0.0036 (14)−0.0200 (13)
C420.065 (2)0.067 (2)0.063 (2)−0.0151 (18)0.0140 (18)−0.0108 (18)
C430.114 (4)0.070 (2)0.059 (2)−0.027 (3)0.019 (2)−0.011 (2)
C440.120 (4)0.059 (2)0.054 (2)−0.006 (2)−0.010 (2)−0.0086 (18)
C450.081 (3)0.095 (4)0.082 (3)0.000 (3)−0.025 (3)−0.005 (3)
C460.055 (2)0.078 (3)0.069 (3)−0.0081 (18)−0.0066 (18)−0.005 (2)
C610.0390 (15)0.0486 (16)0.085 (3)−0.0129 (12)0.0042 (15)−0.0259 (16)
Geometric parameters (Å, °) top
Cl1—C441.747 (5)C41—C421.386 (6)
S2—C21.686 (3)C42—C431.392 (6)
O15—C151.211 (4)C43—C441.370 (9)
N1—C21.359 (4)C44—C451.343 (9)
N1—C61.395 (4)C45—C461.397 (8)
N3—C21.320 (4)C4—H40.9800
N3—C41.461 (4)C16—H16A0.9600
N1—H10.83 (4)C16—H16B0.9600
N3—H30.90 (4)C16—H16C0.9600
C4—C411.525 (5)C42—H420.9300
C4—C51.515 (5)C43—H430.9300
C5—C61.353 (4)C45—H450.9300
C5—C151.469 (4)C46—H460.9300
C6—C611.498 (5)C61—H61A0.9600
C15—C161.501 (5)C61—H61B0.9600
C41—C461.374 (6)C61—H61C0.9600
Cl1···O15i3.332 (4)C16···H61C2.8800
S2···N3ii3.328 (3)C16···H61A2.7700
S2···H46iii2.9200C42···H16Aiv3.0800
S2···H61Aiv3.0700C43···H43viii2.9800
S2···H4iii3.1900C61···H16B2.7100
S2···H3ii2.43 (4)C61···H16C2.9000
S2···H61Bv3.0600H1···O15iii2.06 (4)
O15···N1vi2.882 (3)H1···H61B2.1100
O15···C413.253 (4)H3···S2ii2.43 (4)
O15···C463.348 (6)H4···S2vi3.1900
O15···C61vi3.405 (4)H4···O152.3300
O15···Cl1i3.332 (4)H4···H462.3400
O15···H42.3300H16A···C42vii3.0800
O15···H61Bvi2.5800H16B···C63.0900
O15···H1vi2.06 (4)H16B···C612.7100
N1···O15iii2.882 (3)H16B···H61A2.1600
N3···S2ii3.328 (3)H16C···C612.9000
N1···H422.8200H16C···H61C2.4300
N3···H422.8100H42···N12.8200
C2···C423.366 (5)H42···N32.8100
C6···C423.549 (5)H42···C22.8100
C16···C613.061 (5)H42···C53.0800
C16···C42vii3.552 (6)H43···C43viii2.9800
C41···O153.253 (4)H46···S2vi2.9200
C42···C63.549 (5)H46···H42.3400
C42···C23.366 (5)H61A···S2vii3.0700
C42···C16iv3.552 (6)H61A···C153.0900
C43···C43viii3.492 (7)H61A···C162.7700
C46···O153.348 (6)H61A···H16B2.1600
C61···C163.061 (5)H61B···O15iii2.5800
C61···O15iii3.405 (4)H61B···H12.1100
C2···H422.8100H61B···S2v3.0600
C5···H423.0800H61C···C162.8800
C6···H16B3.0900H61C···H16C2.4300
C15···H61A3.0900
C2—N1—C6124.2 (2)C43—C44—C45121.7 (5)
C2—N3—C4124.3 (3)Cl1—C44—C45119.8 (5)
C2—N1—H1118 (2)C44—C45—C46119.7 (5)
C6—N1—H1118 (2)C41—C46—C45120.8 (4)
C2—N3—H3122 (2)N3—C4—H4108.00
C4—N3—H3113 (2)C5—C4—H4108.00
S2—C2—N3123.2 (3)C41—C4—H4108.00
N1—C2—N3116.3 (3)C15—C16—H16A109.00
S2—C2—N1120.5 (2)C15—C16—H16B109.00
N3—C4—C5110.0 (3)C15—C16—H16C110.00
N3—C4—C41111.2 (3)H16A—C16—H16B109.00
C5—C4—C41111.1 (3)H16A—C16—H16C110.00
C4—C5—C15113.8 (3)H16B—C16—H16C110.00
C6—C5—C15127.1 (3)C41—C42—H42119.00
C4—C5—C6119.1 (3)C43—C42—H42119.00
N1—C6—C5118.6 (3)C42—C43—H43121.00
N1—C6—C61112.4 (3)C44—C43—H43121.00
C5—C6—C61129.0 (3)C44—C45—H45120.00
C5—C15—C16123.5 (3)C46—C45—H45120.00
O15—C15—C5118.3 (3)C41—C46—H46120.00
O15—C15—C16118.2 (3)C45—C46—H46120.00
C4—C41—C46120.9 (3)C6—C61—H61A109.00
C42—C41—C46118.0 (4)C6—C61—H61B109.00
C4—C41—C42121.1 (3)C6—C61—H61C109.00
C41—C42—C43121.2 (4)H61A—C61—H61B109.00
C42—C43—C44118.5 (5)H61A—C61—H61C109.00
Cl1—C44—C43118.5 (4)H61B—C61—H61C109.00
C6—N1—C2—S2169.9 (2)C4—C5—C6—C61−176.4 (3)
C6—N1—C2—N3−9.4 (5)C15—C5—C6—N1−176.0 (3)
C2—N1—C6—C513.7 (4)C15—C5—C6—C612.4 (6)
C2—N1—C6—C61−164.9 (3)C4—C5—C15—O15−12.9 (5)
C4—N3—C2—S2166.0 (3)C4—C5—C15—C16165.2 (4)
C4—N3—C2—N1−14.8 (5)C6—C5—C15—O15168.3 (4)
C2—N3—C4—C530.5 (4)C6—C5—C15—C16−13.7 (6)
C2—N3—C4—C41−93.1 (4)C4—C41—C42—C43178.4 (4)
N3—C4—C5—C6−24.4 (4)C46—C41—C42—C43−2.0 (6)
N3—C4—C5—C15156.7 (3)C4—C41—C46—C45−177.3 (4)
C41—C4—C5—C699.1 (4)C42—C41—C46—C453.1 (7)
C41—C4—C5—C15−79.8 (4)C41—C42—C43—C440.6 (7)
N3—C4—C41—C4253.6 (4)C42—C43—C44—Cl1−177.8 (4)
N3—C4—C41—C46−126.0 (4)C42—C43—C44—C45−0.1 (8)
C5—C4—C41—C42−69.3 (4)Cl1—C44—C45—C46178.7 (4)
C5—C4—C41—C46111.1 (4)C43—C44—C45—C461.1 (8)
C4—C5—C6—N15.3 (5)C44—C45—C46—C41−2.7 (8)
Symmetry codes: (i) −x+1, −y+1, −z; (ii) −x+2, −y+1, −z+1; (iii) x+1, y, z; (iv) x, y+1, z; (v) −x+3, −y, −z+1; (vi) x−1, y, z; (vii) x, y−1, z; (viii) −x+2, −y+1, −z.
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O15iii0.83 (4)2.06 (4)2.882 (3)175 (4)
N3—H3···S2ii0.90 (4)2.43 (4)3.328 (3)172 (3)
C61—H61B···O15iii0.962.583.405 (4)144
Symmetry codes: (iii) x+1, y, z; (ii) −x+2, −y+1, −z+1.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O15i0.83 (4)2.06 (4)2.882 (3)175 (4)
N3—H3···S2ii0.90 (4)2.43 (4)3.328 (3)172 (3)
C61—H61B···O15i0.962.583.405 (4)144
Symmetry codes: (i) x+1, y, z; (ii) −x+2, −y+1, −z+1.
Acknowledgements top

AT thanks the UGC, India, for the award of a Minor Research Project [File No. MRP-2355/06(UGC-SERO), Link No. 2355, 10/01/2007]. RJB acknowledges the NSF MRI program (grant No. CHE-0619278) for funds to purchase an X-ray diffractometer.

references
References top

Atwal, K. S., Rovnyak, G. C., Kimball, S. D., Floyd, D. M., Moreland, S., Swanson, B. N., Gougoutas, J. Z., Schwartz, J., Smillie, K. M. & Malley, M. F. (1990). J. Med. Chem. 33, 2629–2635.

Atwal, K. S., Swanson, B. N., Unger, S. E., Floyd, D. M., Moreland, S., Hedberg, A. & O'Reilly, B. C. (1991). J. Med. Chem. 34, 806–811.

Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.

Grover, G. J., Dzwonczyk, S., McMullen, D. M., Normadinam, C. S., Sleph, P. G. & Moreland, S. J. (1995). J. Cardiovasc. Pharm. 26, 289–294.

Kappe, C. O. (1993). Tetrahedron, 49, 6937–6963.

Oxford Diffraction (2008). CrysAlis CCD and CrysAlis RED. Oxford Diffraction Ltd, Abingdon, England.

Patil, A. D., Kumar, N. V., Kokke, W. C., Bean, M. F., Freyer, A. J., De Brosse, C., Mai, S., Truneh, A., Faulkner, D. J., Carte, B., Breen, A. L., Hertzberg, R. P., Johnson, R. K., Westley, J. W. & Potts, B. C. M. (1995). J. Org. Chem. 60, 1182–1188.

Rovnyak, G. C., Kimball, S. D., Beyer, B., Cucinotta, G., Dimarco, J. D., Gougoutas, J. Z., Hedberg, A., Malley, M., McCarthy, J. P., Zhang, R. & Moreland, S. (1995). J. Med. Chem. 38, 119–129.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.

Spek, A. L. (2009). Acta Cryst. D65, 148–155.

Stefani, H. A., Oliveira, C. B., Almeida, R. B., Pereira, C. M. P., Braga, R. C., Cella, R., Borges, V. C., Savegnago, L. & Nogueira, C. W. (2006). Eur. J. Med. Chem. 41, 513–518.